Hydroxychloroquine and Temozolomide in Treating Patients With Metastatic or Unresectable Solid Tumors

NCT00714181 | Completed Phase 1 DMC

• 2 other identifiers: CDR0000600329UPCC-12907
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as hydroxychloroquine and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of hydroxychloroquine when given together with temozolomide in treating patients with metastatic or unresectable solid tumors.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose of hydroxychloroquine

Secondary Outcomes (2)

• Toxicity rates

• Pharmacodynamic and pharmacokinetic correlative endpoints

Interventions

hydroxychloroquine DRUG

temozolomide DRUG

TdT-mediated dUTP nick end labeling assay GENETIC

western blotting GENETIC

electron microscopy OTHER

high performance liquid chromatography OTHER

immunoenzyme technique OTHER

immunohistochemistry staining method OTHER

laboratory biomarker analysis OTHER

mass spectrometry OTHER

pharmacological study OTHER

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed solid tumor * Metastatic or unresectable disease * Refractory to standard therapy or no standard therapy exists * Measurable disease by RECIST criteria * Brain metastases allowed provided patient completed radiotherapy (if radiotherapy was clinically indicated at the time of diagnosis) AND discontinued steroids prior to study enrollment PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * WBC ≥ 3,000/mm³ * Absolute granulocyte count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Serum creatinine ≤ 2.0 times upper limit of normal (ULN) * Total bilirubin ≤ 1.5 times ULN (\< 3.0 times ULN in the presence of Gilbert's disease) * AST and ALT ≤ 2.5 times ULN (≤ 5.0 times ULN in the presence of liver metastases) * aPTT normal * INR ≤ 1.5 (if on anticoagulation, INR must be \< 1.5 prior to starting anticoagulation) * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * HIV negative * No porphyria * No psoriasis, unless the disease is well controlled and patient is under the care of a specialist who agrees to monitor the patient for exacerbations * No previously documented macular degeneration or diabetic retinopathy * No concurrent serious illness including, but not limited to, any of the following: * Ongoing or active infection requiring parenteral antibiotics * Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, myocardial infarction, or unstable angina) * New York Heart Association class II-IV congestive heart failure * Serious cardiac arrhythmia requiring medication * Peripheral vascular disease ≥ grade 2 within the past year * Psychiatric illness/social situation that would limit compliance with study requirements * No other concurrent malignancies, other than basal cell skin cancer, squamous cell skin cancer, carcinoma in situ of the cervix, or ductal or lobular carcinoma in situ of the breast PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from all prior therapy * The following prior therapy is allowed in the adjuvant or metastatic disease setting: * Immunotherapy (interferon, aldesleukin, or sargramostim \[GM-CSF\]) * Chemotherapy, either as a single-agent or as combination therapy * Vaccine therapy * Targeted or biological therapy * Chloroquine derivatives * At least 4 weeks since prior active immunotherapy (aldesleukin, interferon, or ipilimumab) * At least 4 weeks since prior chemotherapy * At least 2 weeks since prior oral targeted therapies * More than 4 weeks since prior and no other concurrent investigational anticancer therapy (except for vaccines) * No prior temozolomide * Prior radiotherapy allowed * If radiotherapy has been administered to a lesion, there must be radiographic evidence of progression of that lesion in order for that lesion to constitute measurable disease or to be included in the measured target lesions * No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, phenobarbital, primidone, or oxcarbazepine), rifampin, or Hypericum perforatum (St. John's wort) * No other concurrent anticancer therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

MeSH Terms

Interventions

Hydroxychloroquine; Temozolomide; Blotting, Western; Microscopy, Electron; Chromatography, High Pressure Liquid; Immunoenzyme Techniques; Immunohistochemistry; Mass Spectrometry

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Electrophoresis; Chemistry Techniques, Analytical; Investigative Techniques; Electrochemical Techniques; Immunoblotting; Immunoassay; Immunologic Techniques; Molecular Probe Techniques; Microscopy; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Chromatography, Liquid; Chromatography; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Histological Techniques

Study Officials

• Ravi Amaravadi, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2008
• First Posted: July 14, 2008
• Study Start: June 1, 2008
• Primary Completion: July 1, 2011
• Study Completion: June 1, 2013
• Last Updated: February 18, 2016

Record last verified: 2016-02

Locations

US (1)